Is JUP p.Ser182= (c.546G>A) pathogenic?

JUP p.Ser182= (c.546G>A) is classified Conflicting classifications of pathogenicity in JUP (ClinVar, Conflicting submitters, 15 submitters; last evaluated 2026-03-27). Rare (popmax 0.14%, eas); Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Ser182= (c.546G>A)?

JUP p.Ser182= (c.546G>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy (ClinVar).

How common is JUP p.Ser182= (c.546G>A) in the general population?

JUP p.Ser182= (c.546G>A) is rare (popmax 0.14%, eas) (gnomAD).

JUP p.Ser182=

c.546G>A · rs202038498 · VCV227451

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

rare (popmax 0.14%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.7
Overall
CADD	1.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.14% East Asian · 63/44,852 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.0123% 198/1,609,536 alleles · rare exomes 162/1,457,274 · genomes 36/152,262 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.14%	712
Remaining individualsnot grpmax-eligible	0.104%	960
African / African-American	0.0213%	4,690
Admixed American	0.0167%	5,999
South Asian	0.00988%	10,117
European (non-Finnish)	0.00297%	33,708

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: JUP
Protein: p.Ser182=
Coding: c.546G>A
MANE Select: NM_002230
dbSNP: rs202038498
Type: single nucleotide variant
Location: chr17:41769130 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 182: the 'interaction with dsc1 and dsg1' region; a modified residue (phosphoserine)

Full JUP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy dilated cardiomyopathy Naxos disease arrhythmogenic right ventricular dysplasia 12

Similar variants

JUP p.Ser182Ter Pathogenic ★ same residue
JUP p.Ser182Ala Uncertain significance ★ ⚠ same residue
JUP p.Ser182Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
JUP c.1773+3G>A Uncertain significance ★★ same condition
JUP c.468+4T>C Uncertain significance ★★ same condition
JUP c.707+5C>A Uncertain significance ★★ same condition
JUP c.-1G>A Uncertain significance ★★ same condition
JUP c.*1026G>A Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/jup-p-ser182 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown